Alkoxy-caffein and process of making same.



UNITED STATES ATENT FFICE.

FRITZ ACH, OF MANNHEIM, GERMANY, ASSIGNOR TO 0. F. BOEHRINGER 85 SOEHNE,OF WALDHOF, GERMANY.

ALKOXY-CAFFEIN AND PROCESS OF MAKING SAME.

SPECIFICATION formingpart of Letters Patent No. 667,380, dated February5, 1901.

Application filed April 16, 1898- b'erial No. 677,85 8. (Specimens.)

T0 (0Z7 whom, it may concern:

Be it known that I, FRITZ ACH, a citizen of the German Empire, residingat Mannheim, in the Empire of Germany, have invented certain new anduseful Improvements in the Art of Preparing Alkoxy-Catfeins; and I dohereby declare the following to be a full, clear, and exact descriptionof the invention, such as will enable others skilled in the art to whichit appertains to make and use the same.

The present invention relates to the art of preparing alkoxy-caifeins;and its object in particular is the production of3*-alkoxy-caffeins-that is to say, such substituted caffeins in whichthe group (J H OOI-I is substituted for the CH in the position (3) ofthe caffein molecule, thus cH,.N oo

The invention consists, broadly, in treating 3-alkoXy-S-chloro-cadeinwith reducing agents; and it, moreover, consists in such furtherfeatures, steps, and methods as will be hereinafter set forth, andpointed out in the claims.

I will now give a detailed description of my invention and the manner inwhich it may be carried out.

In preparing the 3-alkoXy-caffeins I start from3'-alkoxy-S-chloro-caffein, which in turn is prepared from3-8-dichloro-caffein. As both of these compounds and their methods ofpreparation have not heretofore been described, but form thesubject-matter of my applications, Serial Nos. 677,857 and 677,854,respectively, filed concurrently herewith, I will first give adescription of these for the purpose of a full disclosure.

Preparation 0f3-8-dichZoro-ca jein.-I take twenty-three parts, byweight, of dried chlorocaffein and heat them to from 150 to 155centigrade in a digester, together with thirty parts, by weight,(corresponding to one and one-half molecules per molecule of chloro--caifein,) of phosphorus-penta-chlorid and one hundred parts, by volume,of phosphorus-oxychlorid, maintaining this temperature for from eight tonine hours. The mass is then allowed to cool, when it will be found thatno more pressure exists in the vessel and that a reddish-brown solutionhas been formed containing colorless acicular crystals in suspension.The entire product of the reaction is then well evaporated in cacao,whereby a reddish-brown resinous substance of a tough consistency willbe obtained. Bydissolving this product in ether and allowing it to standfor some time (about eight to fourteen days) a slightly-coloredcrystalline mass is obtained, which is then triturated with a little(about one-half part) cold benzol, siphoned off or decanted, and thenredissolved in and recrystallized from warm ether. The new compound3-8-dichloro-caffein or 3-chloro-methyl-1-7- dimethyl-S-chloro-xanthinis so obtained in colorless shining well-formed crystals whose analysisgives figures corresponding to the formula O H N O Cl This new compoundmelts at 144 to l45.5 centigrade, forming a colorless liquid. Withchlorin-water it gives the mureXid test. It is readily soluble in coldchloroform, acetone, acetic ether, benzene, and in warm ether andalcohol, but soluble with difiiculty in cold water. On boiling the samewith alcohol or water hydrochloric acid is split off,3-oxy-8-chloro-caifein or 3-oxymethylene-l-7dimethyl-8chlore-Xanthin orderivatives of the same being formed.

In preparing the 3-methoxy-Schloro-caffein it is not necessary to startwith the 3-8-dichloro-cafiein in its pure and crystalline condition; butI may employ directly the syrup or resinous substance which, accordingto the above, serves for the production of the crystalline product3-8-dichloro-cafiein. Such syrup is boiled, together with about twentytimes its weight of absolute methylalcohol, for from five to six hoursin a reflux cooler. The alcohol is then distilled off completely, andthe residue is taken up with ether and washed with water to remove thehydrochloric acid. The ether is evaporated and a little (about twoparts) methyl alcohol is poured over the residue, which after some timebegins to solidify to a crystalline mass. This crystalline mass is thenredissolved in methyl-alcohol and recrystallized therefrom, whereby thenew body 3'-methoxy-8-chlorocaffein is obtained in the form of fineshining needles felted together asbestos-like. An analysis of them givesfigures corresponding to the formula O H N O Ol, the constitution of thenew compound being represented in the structural formula 0H,... oo

oo o-NcH H o.c1

This new compound 3-methoxy-S-chloro-caffein melts at 129 to 130centigrade. With dilute nitric acid or with chlorin-water it gives astrong murexid reaction. It is read ily soluble in boiling water, hotalcohol, benzol, acetone, acetic ether, and chloroform. It is, moreover,readily soluble in fuming hydrochloric acid. If this solution is heatedfor some time on the water-bath, however, decomposition takes place,chloro-paraxanthin, which separates in the form of coarse colorlessprisms, being formed, attended by a splitting off of formic aldehyde andmethylchlorid.

Preparation of 3- methoacy cafi e'in.-This new compound is obtained by areduction of the 3 methoxy- 8 chloro caifein just described. If one partof this methoXy-chlorocaffein is heated to from 105 to 110 centigradeunder pressuret'. 6., in a closed Vesseltogether with two parts ofzinc-dust, twenty parts of water, and one part, by volume, ofconcentrated ammonia solution, and this temperature is maintained forfrom four to five hours while agitating the mixture, a completereduction to 3methoxy-caifein is effected. For isolating the new bodythe liquid while still hot is filtered from the zincdust, and thefiltrate after having been evaporated is repeatedly (two or three times)shaken, together with chloroform. The residue after evaporation isredissolved and crystallized from benzene, whereby the 3-methoxy-caffein is obtained in the form of shining colorless prisms oras fine felted needles. On drying at 105 centigrade an analysis of thesame shows that the formula O H N O or structurally is to be assigned tothe new compound. The

form and is best recrystallized from warm ether or boiling ligroin. Froman aqueous solution it is precipitated in the form of fine needles byalkaline lyes.

By heating the same with hydrochloric acid 3-methoxy-caffein isconverted into paraxanthin.

In treating other 3-alkoxy-8-chloro-caffeins in a similar manner to theabove the corresponding 3'-alkoxy-caffeins will be obtained.

The new 3-alkoXy-cafieins have the following properties: They arecrystallizable derivatives of caffein. They are readily soluble in hotwater and in alcohol. On heating them with mineral acids the group OH O-C 11 bound to the N-atom in the position 3 is split off.

What I claim, and desire to secure by Letters Patent of the UnitedStates, is-

1. In the art of preparing alkoxy-caffeins, the process which consistsin acting upon 3-alkoXy8-chloro-caifeins with a reducing agent.

2. The process which consists in treating 3'-methoxy-S-chloro-caffeinwith a reducing agent.

3. The process which consists in heating 3-methoXy-8-chloro-catfein withzinc-dust and ammonia under pressure, and in the proportions set forth.

4. The process which consists in heating 3'-methoXy-8-chloro-caffeinwith zinc-dust and ammonia under pressure in the proportions set forth,then separating the resultant liquid from the zinc-dust and evaporatingthe same and treating the residue with chloroform.

5. The process which consists in heating 3-methoxy-B-chloro-caifein withzinc-d ust and ammonia under pressure, in the proportions set forth,then separating the resultant liquid from the zinc-dust and evaporatingthe same and treating the residue with chloroform, and finallyevaporating the chloroform and crystallizing the residue from benzol.

6. As a new chemical compound, a 3'-al-.

koxy-cafiein which is distinguished from caffein proper by having thegroup (J H QOH substituted for the methyl in the position 3; arecrystallizable derivatives of caffein, readily soluble in hot water andin alcohol and which on being heated with mineral acids split off thegroup CI-I -OO H 7. As a new chemical compound 3-methoxy-cafiein whichhas the formula above given and which is distinguished by the followingcharacteristics: it crystallizes in the form of shining colorless prismsor fine felted needles, which melt at from 121 to 123, centigrade, andsublime at higher temperatures; it gives the murexid reaction withchlorin-water; it is readily soluble in cold water, alcohol, benzene,acetone or chloroform.

In testimony whereof I affix my signature in presence of two witnesses.

FRITZ ACH.

Witnesses:

LORENZ ACH, GUSTAV HEINRICHS.

